Joint Pain And SwellingCommon Rheumatologic Concerns

ROBERT VALENTE MDARTHRITIS CENTER OF NEBRASKA LINCOLN, NE

I have no financial disclosures or conflicts of interest to report

1/3rd of All Primary Care Visits Involve a Musculoskeletal Complaint.

Do You See Patients with Joint and Muscle Aches and Pains?DO YOU ALWAYS FEEL COMFORTABLE TRIAGING THESE PATIENTS?

Common Arthritis Questions• Is it inflammatory arthritis ?

• Distinguishing RA from OA

• What does this + ANA mean?• Distinguishing CTD from chronic pain and fibromyalgia

Case 1DISTINGUISHING INFLAMMATORY ARTHRITIS FROM OSTEOARTHRITIS

Case 1: The Reluctant Contractor67 yo Male Contractor• Previous hx of LBP, neck pain

chronic plantar fasciitis• 2 yrs previous, pneumonia, Rx included prednisone. Joints felt

wonderful. • 2+ yrs of polyarthralgia, 3 ibuprofen QID, otherwise too stiff to

get out of bed• No F/C/S, no wt loss. No rash or sun sensitivity, no dry eyes, eye

inflammation, pleurisy, SOB, Cough, or GI distress. No numbness, Raynauds. No hx STD, kidney stones or gout. No hx of cancer, recent infection.

• Dad with seropositive RA • Pain score 6, AM stiff 10 min

What features of the Patient History suggest inflammatory polyarthritis? A. 10 min of morning stiffness

B. Hx of Back pain and plantar fasciitis?

C. Trial of prednisone made everything better

D. Needs 12 ibuprofen a day, or too stiff to get out of bed and dad had rheumatoid arthritis

DDx of Polyarticular Pain• Polyarthritis: Chronic and Acute (viral)• Reactive arthritis• Fibromyalgia• Multiple site Bursitis/Tendonitis• Hypothyroidism• Metastasis• Depression• Neuropathic pain• Metabolic/inherited bone diseases (osteomalacia, osteogenesis

imperfecta)

“The evaluation of the adult with polyarticular pain”Shmerling RH, ed Wolters Kluwer, May 2018

Case 1 Physical Exam• Rapid 3 = 7.5• Moderate OA hands, 1st and

3rd MCPS, 1st CMCs, AC joints, L knee, B PF joints, toes

• Bilateral Rotator cuff dysfunction

• Normal Achilles, No sausage digits

• Normal L-spine motion (finger to floor distance 2 inches)

• 17 swollen, 20 tender joints

Can you tell if a joint is swollen?

• Yes• No

Case 1LAB AND X-RAY RESULTS

• Normal: CBC, ESR, CRP, Chemistries, urine

• -RF, -CCP, - ANA

• X-ray hands C/W osteoarthritis, Moderate (nodal pattern)

Rheumatoid Arthritis:Radiographic Abnormalities

• Soft tissue swelling

• Symmetric joint involvement

• Peri-articular osteoporosis

• Symmetric joint space narrowing

• Marginal erosions

• Deformity – Fibrous ankylosis

Question

Does this 67 yo Male Contractor have inflammatory Arthritis?A. Yes

B. No

The Case for Inflammatory Arthritis • SX > 6 weeks

• Prolonged AM stiffness

• SX better with ibuprofen

• + family hx of Sero+ RA

• 17 Swollen joints on PE

The Case Against Inflammatory Arthritis• Patient is 67 yo, and a laborer with lots of OA

• No CTD disease features

• No inflammatory bowel sx

• No psoriasis

• No STD risks, no Gout/stone

• Normal ESR, CRP

• Negative ANA, RF, CCP

• X-rays show osteoarthritis without erosions, Ca++, etc

Does Negative RF, CCP, Normal ESRAffect Your DecisionA. YES

B. NO

The Key: SYNOVITIS

Rheumatoid Arthritis Osteoarthritis

Laboratory Testing to Discriminate Between RA and Non-RA in Patients With Early Arthritis

Anti-CCP * 48 96 84 81

IgM RF * 54 91 74 81

Anti-CCP or RF 63 88 72 83

Anti-CCP and RF

39 98 91 78

Sensitivity (%) Specificity (%) PPV (%) NPV (%)

*Anti-CCP and IgM RF were determined by enzyme-linked immunosorbent assay (ELISA).CCP = cyclic citrullinated protein; PPV = positive predictive value; NPV = negative predictive value. Visser H, et al. Best Pract Res Clin Rheum. 2005;19:52–72.

II.14

Elevated ESR had a PPV of only 17% for RA

Early Undifferentiated Polyarthritis: What Matters? Synovitis (especially @ 3 Mo)% Patients Receiving DMARDs at 12 Months

RF + RF -

Synovitis 70 43

No synovitis

40 15

↑ CRP ↑ CRP

RF +

Synovitis 62 80

No synovitis

0 33

RF +

SE +

Synovitis 60

No synovitis

0

RF + RF -

Synovitis 75 70

No synovitis

0 2

↑ CRP ↑ CRP

RF +

Synovitis 69 100

No synovitis

0 0

RF +

SE +

Synovitis 60

No synovitis

0

Characteristics at Baseline

Characteristics at Month 3

SE = possession of ≥ 1 allele of shared epitope (HLA-DR1,4,10); UPA = undifferentiated polyarthropathy. CRP = C-reactive protein level ≥ 10 mg/L.Quinn MA, et al. Arthritis Rheum. 2003;48:3039–3045.

What Trumps What?

SYNOVITIS !

2010 ACR/EULARRA Classification Criteria ≥ 6 points = RA• 1 med or large joint swelling = 0 points

• 2 – 10 med or large joints swollen = 1 point

• 1 – 3 small joints swollen = 2 points

• 4 – 10 small joints swollen = 3 points

• > 10 small joints swollen = 4 points

• - RF, - CCP = 0 points

• + RF or + CCP (low titer 2-3 x normal) = 2 points

• +RF or + CCP high titer = 3 points

• Duration of synovitis > 6 weeks = 1 point

• Abnormal CRP or ESR = 1 point A & R, Aug 2010

• Treatment Goals• Make the patient feel as normal

as possible

• Prevent bony damage/disability

• Avoid toxicity

• Cost effectiveness

• Use standardized scoring to measure RA disease activity

• Treat to Target (low disease activity)

2015 ACR Guideline for the Treatment of Rheumatoid Arthritis, Arthritis Rheumatol. 2016 Jan;68(1):1-26

Case 1: Dx = Seronegative RA

Sev

erit

y (a

rbit

rary

un

its)

Graph: Adapted from Kirwan JR. J Rheumatol. 2001;28:881–886.Photo: Copyright © American College of Rheumatology.

The Progression of RA -Why Do We Need To Dx Early?

0Duration of Disease (years)

5 10 15 20 25 30

Early Intermediate LateInflammationDisabilityJoint Damage

Window of Opportunity

Very Early RA (VERA) vs Late Early RA (LERA)Impact of DMARD Therapy on ACR Response Rates

65

50

35

70

6055

2015

0

40

2520

0

10

20

30

40

50

60

70

803 months 36 months

% o

f P

atie

nts

ACR-20 ACR-50 ACR-70 ACR-20 ACR-50 ACR-70

VERA patients

LERA patients

**

*

**

*P < 0.05 for LERA vs VERA.VERA = patients presented within 3 mo of symptom onset; LERA = patients presented between 9 months and 3.5 years after symptom onset (median of 12 months). All patients were naive to treatment with DMARDs.Nell, VPK et al. Rheumatology. 2004;43:906–914.

II.22

Case1: Treatment• Problems with dysphagia

• Initially did not use / continue NSAID• Upper endoscopy negative• Started back on Ibuprofen 600 mg TID

• Prednisone 5 mg Q AM (with taper beginning at 8 wks

• Methotrexate, increasing dose to 20 mg po Q week

• Folic acid

• @ 2 mo Rapid 3 was 4, down from 7.5, AM stiff 15 min

• Swollen joint count 11, down from 17

This Photo by Unknown Author is licensed under CC BY-NC-ND

Case 2WHEN DOES A POSITIVE ANA MEAN SOMETHING??WHEN TO AVOID CHECKING AN ANA!

Case 2: The Stiff Daycare Provider• 23-year-old nonsmoking female daycare provider• Onset of pain and stiffness and swelling in her hands and wrists

beginning February 2017. Compromised activities of daily living.• Morning stiffness that would last up to 4 hours• Primary care evaluation documented new onset

hypothyroidism. No improvement in joint symptoms with T4• Trial of prednisone with prompt but temporary benefit.

Minimal benefit with diclofenac• Mother notices puffy fingers• At the same time, patient’s develops classic white

attacks/Raynaud’s phenomenon. No other formal CTD sx.(No SOB, swallowing difficulty, Dry eyes, oral ulcers, numbness, rash)

What historical features suggest inflammatory arthritis?A. Pain and stiffness in the hands

B. Prednisone helped temporarily, diclofenac without benefit

C. Puffy, swollen fingers noted by mom

D. Raynaud’s phenomenon

E. New onset hypothyroidism

F. All of the above

Fibromyalgia • Muscle attachment pain

• Hurt all over (Large > small joints)

• All day stiffness

• No swollen joints

• Normal inflammatory markers

• Other complaints• Fatigue, cognitive problems, • Paresthesia, headache• Irritable bowel and bladder

+ANA ≠ inflammatory arthritis

Predicting Pain in OA ptsafter TKA and THA• Outcomes

• Post op opioid consumption• Pain relief @ 6mo

• 9 mg > Morphine requirements for each point higher “FM-ness”

• 20% less likely to reach 50% less pain after arthroplasty with each point higher “FM-ness”

Brummett, etal. Anesthesiology, 2013

Fibromyalgia-ness (FM-ness)Calculated with the Polysymptomatic Distress Scale

DDx of Polyarticular Pain• Polyarthritis: Chronic and Acute (viral)• Reactive arthritis• Fibromyalgia• Multiple site Bursitis/Tendonitis• Hypothyroidism• Metastasis• Depression• Neuropathic pain• Metabolic/inherited bone diseases (osteomalacia, osteogenesis

imperfecta)

“The evaluation of the adult with polyarticular pain”Shmerling RH, ed Wolters Kluwer, May 2018

BUT…

This is Polyarthralgia/itis + Something ELSEFORMAL CTD / SLE

HEPATIT IS • Polyarthritis +

• Raynauds• Polyserositis• Rash• Sun sensitivity• Dry Eyes• Multiple Miscarriages• DVT• Seizures• Renal disease• Cytopenias

VASCULIT IS

• Polyarthritis +• New HA, visual changes• Claudication• Nephritis• Pulmonary infiltrates • Pulmonary hemorrhage• Neuropathy• Purpura / ulcers

SPONDY / IBD/PSORIATIC

• Polyarthritis + • Inflammatory back

pain• Iritis• Psoriasis • Inflammatory Bowel

disease• Hx of dysentery or

STD

Case 2: Physical Exam• Wt 134#, BP 96/65, Pain 8.5• Skin: puffy fingers

+++ nailfold capillary changes- telangiectasia, scleroderma-psoriasis, Nodules

• CV: no murmur, 4+ pulses, - Allen’s test bilaterally

• Lungs, Abd, Neuro, Extremitiesall normal. No edema

• Raynaud’s phenomenon• 18 swollen and tender joints

Case 2: Lab and X-ray• Lab from home

• Normal ESR, CRP, TSH, Lyme titer, B12, Vit D 26.8

• Lab after Rheum Visit• Normal Hepatitis profile B,C• Normal CBC, SPEP

Chemistries (Cr, AST, CPK), urinalysis

• - ANA, ++++RF, complement

• CXR normal

• Hand x-ray normal except for soft tissue swelling

Case 2:Does this patient have

A. Fibromyalgia?B. Rheumatoid Arthritis ?C. Thyroid myxedema ?D. Myositis sine Myositis?E. Scleroderma?

Additional Studies• + PM/ScL, + RNA pol III, - ENA (ACA, Scl-70, RNP), - anti-

myositis Abys

• Echo normal

• PFTs: FVC 65, FEV1 64 DLCO 57, TLC 60(Restrictive Lung Disease)

She has Scleroderma / systemic sclerosis• Scleroderma

• Inflammatory polyarthritis

• Raynaud’s phenomenon

• Nailfold capillary changes

• + RNA Polymerase III

• + PM/ScL

• +RF

• Restrictive lung disease

Systemic Sclerosis (SSc)Subsets of SSc are :

• Diffuse cutaneous SSc (dcSSc)

• Limited cutaneous SSc (lcSSc) CREST

• SSc sine scleroderma, in which patients have only internal organ involvement

• Environmentally-induced scleroderma

• Overlap syndromes, in which features of SSc coexist with elements of other rheumatic disorder

• 70% of Systemic Sclerosis can be serologically defined.

• Serologic markers can separate Diffuse systemic sclerosis (+Scl-70) from limited /CREST(+Centromere)

• + RNA pol III puffy fingers, contracture, high risk of scleroderma renal crisis, 1st 5 years heightened risk of interstitial lung disease, increased risk of cancer

“Overview and classification of scleroderma disorders”, Denton, CP, ed Wolters Kluwer, November 2016

Scleroderma Mortality

Czirjak, etal, Survival and cause of death in 366 Hungarian patients with Systemic Sclerosis. Ann Rheum Diseases 2008, 67:59-63

Systemic Sclerosis Treatment• Arthritis and puffy fingers

/scleroderma• Methotrexate, Hydroxychloroquine,

Mycophenolate, gabapentin, pregabalin

• Avoid prednisone > 5 mg/day

• Interstitial lung disease• Corticosteroids (short term)• Mycophenolate, Cyclophosphamide• Autologous bone marrow transplant

• Renal• ACE inhibitors, …

• Raynaud's• nifedipine, amlodipine,

(dihydropyridines),phosphodiesterase-5 inhibitors, topical nitrate, fluoxetine, Botox, sympathectomy, endothelin receptor antagonists, prostacyclin, clopidogrel

• Pulmonary Hypertension• Anticoagulation, endothelin receptor

antagonists, phosphodiesterase-5 inhibitors, prostacyclin (IV and oral)

• Esophageal dysmotility, esophagitis and stricture, bacterial overgrowth • (symptomatic , antibiotics-Rifaximin)

Case 2• Hydroxychloroquine

• Mycophenolate

• Prednisone 5 mg

• Pregabalin

• Omeprazole

• IUD (not BCPs)

• PFTs stabilized after 9 mo

• BPs normal

• 14 swollen joints• 30 min AM stiff, Pain score 7

• No pulmonary HTN as of now

Summary• Does the patient have Inflammatory Arthritis?

Is there synovitis on examination?

• Does the patient have a CTD / Lupus?Is there synovitis?Is there something else? Rash, renal disease, serositis, Raynaud's, Severe dry eyes, cytopenia's

Team Valente